Background 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are potent inhibitors of cholesterol biosynthesis. They have been reported to have anti-inflammatory and/or immunomodulatory as well as prophylactic and therapeutic effects in collagen-induced arthritis models. Bone erosion is a central feature of rheumatoid arthritis and is associated with disease severity and poor functional outcome.
Objectives This study was designed to define the effect of statins on IL-1β-induced osteoclastogenesis and to elucidate the underlying mechanisms.
Methods Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to differentiate them into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1β or atorvastatin. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. The molecular mechanisms of the above effects of atorvastatin on osteoclastogenesis were investigated using RT-PCR and immunoblotting for osteoclast specific molecules.
Results Atorvastatin significantly reduced the number of TRAP-positive multinucleated cells as well as the bone resorption area. Atorvastatin also downregulated the expression of NFATc1 mRNA and inhibited the expression of osteoclast-specific genes. A possible underlying mechanism may be that atorvastatin suppresses the degradation of the inhibitors of NF-κB and blocks the activation of c-JUN N-terminal kinase, extracellular signal-regulated kinase, and p38, thus implicating the NF-κB and MAPK pathway in this process.
Conclusions These results indicate that atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases
Disclosure of Interest None declared
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